Ofatumumab vs Physician's Choice in Subjects With Bulky Fludarabine-Refractory Chronic Lymphocytic Leukemia - Full Text View

Purpose

The purpose of this study is to confirm the clinical benefit observed in the pivotal registration study, Hx-CD20-406. The Committee for Medicinal Products for Human Use (CHMP) required that a randomized study be conducted in CLL patients with bulky fludarabine-refractory disease as a specific obligation for grant of conditional approval for ARZERRA™ in the European Union (EU). This study will compare ofatumumab with the physicians' choice of therapy.

Condition	Intervention	Phase
Leukaemia, Lymphocytic, Chronic	Drug: Ofatumumab Drug: Physicians' Choice	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Factorial Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	An Open Label, Multicenter Study Investigating the Safety and Efficacy of Ofatumumab Therapy Versus Physicians' Choice in Patients With Bulky Fludarabine-Refractory Chronic Lymphocytic Leukaemia (CLL)

Resource links provided by NLM:

MedlinePlus related topics: Chronic Lymphocytic Leukemia Leukemia

Drug Information available for: Fludarabine Fludarabine phosphate Ofatumumab

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

Progression-free survival [ Time Frame: Approximately 44 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall response rate [ Time Frame: Approximately 44 months ] [ Designated as safety issue: No ]
Overall survival [ Time Frame: Approximately 44 months ] [ Designated as safety issue: No ]
The number of patients with adverse events as a measure of safety and tolerability [ Time Frame: Approximately 44 months ] [ Designated as safety issue: Yes ]
Changes in patient reported outcome measures [ Time Frame: Approximately 44 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	120
Study Start Date:	April 2011
Estimated Study Completion Date:	March 2018
Estimated Primary Completion Date:	March 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Ofatumumab Biological	Drug: Ofatumumab Ofatumumab IV, initial dose 300 mg, followed 1 week later with 2000 mg once weekly for 7 weeks, followed 4 weeks later by one infusion of 2000 mg every 4 weeks for 4 infusions, for a total of 12 infusions over 24 weeks. After 24 weeks of ofatumumab treatment, patients who have achieved at least stable disease or better, and whom the investigator would deem appropriate for the therapy to continue, would undergo a second randomisation (2:1) to either 1) an additional ofatumumab dose regimen of 2000 mg once every 4 weeks for up to an additional 24 weeks, or 2) no further therapy (i.e. observation only).
Active Comparator: Physicians' Choice Physicians' choice of treatment	Drug: Physicians' Choice Non-ofatumumab containing regimen as per physicians' choice for up to 6 months. Permitted therapies include treatments approved for CLL, and well established standards of care for CLL.

Arms

Assigned Interventions

Experimental: Ofatumumab

Biological

Drug: Ofatumumab

Ofatumumab IV, initial dose 300 mg, followed 1 week later with 2000 mg once weekly for 7 weeks, followed 4 weeks later by one infusion of 2000 mg every 4 weeks for 4 infusions, for a total of 12 infusions over 24 weeks. After 24 weeks of ofatumumab treatment, patients who have achieved at least stable disease or better, and whom the investigator would deem appropriate for the therapy to continue, would undergo a second randomisation (2:1) to either 1) an additional ofatumumab dose regimen of 2000 mg once every 4 weeks for up to an additional 24 weeks, or 2) no further therapy (i.e. observation only).

Active Comparator: Physicians' Choice

Physicians' choice of treatment

Drug: Physicians' Choice

Non-ofatumumab containing regimen as per physicians' choice for up to 6 months. Permitted therapies include treatments approved for CLL, and well established standards of care for CLL.

Detailed Description:

Patients with CLL that is refractory to fludarabine have few treatment options and a poor prognosis. There is a continued need for new therapies for these CLL patients, as demonstrated by the limited responses and substantial toxicities with existing therapies. This is supported by the lack of a consensus around standard of care treatment for CLL patients with bulky fludarabine-refractory disease. The objective of this study is to confirm the response rate and disease control in the refractory setting through a controlled trial comparing ofatumumab with the physicians' choice of therapy in fludarabine-refractory, bulky lymphadenopathy patients. After 24 weeks of treatment with ofatumumab, patients will be further randomized to either extended ofatumumab treatment or observation. Patients on the physicians' choice arm will have the option of receiving ofatumumab if they experience progressive disease.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Adults with documented diagnosis of active CLL requiring treatment
Bulky lymphadenopathy, defined as at least 1 lymph node >5 cm
Must be refractory to fludarabine treatment
Age 18 yrs or older
At least 2 prior therapies for CLL
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Signed written informed consent

Exclusion Criteria:

Prior allogeneic stem cell transplant at any time, or autologous stem cell transplant within 6 months
Treatment with any unapproved drug substance or experimental therapy within 4 weeks, or currently participating in another interventional clinical study
CLL transformation, prolymphocytic leukemia, or central nervous system (CNS) involvement of CLL
Active autoimmune hemolytic anemia (AIHA) requiring treatment except if associated with progressive disease requiring anti-CLL treatment
Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment
Human immunodeficiency virus (HIV) positive
Significant concurrent, uncontrolled medical condition
Other past or current malignancy (with the exception of basal cell carcinoma of the skin or in situ carcinoma of the cervix or breast) unless the tumor was successfully treated with curative intent at least 2 years prior to trial entry
Non-protocol corticosteroid usage except a maintenance dose corresponding to less than or equal to 10 mg prednisone
Abnormal lab values: Creatinine > 2.0 times upper normal limit (unless normal creatinine clearance), or total bilirubin > 2.0 times upper normal limit (unless due to liver involvement of CLL or due to Gilbert's syndrome), or alanine transaminase (ALT) > 2.5 times upper normal limit (unless due to liver involvement of CLL)
Known or suspected hypersensitivity to ofatumumab
Lactating or pregnant women or female patients of child-bearing potential (or male patients with such partners) not willing to use adequate contraception

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01313689

Contacts

Contact: US GSK Clinical Call Center

877-379-3718

GSKClinicalSupportHD@gsk.com

Show 63 Study Locations

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

No publications provided

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT01313689 History of Changes
Other Study ID Numbers:	114242
Study First Received:	March 10, 2011
Last Updated:	June 6, 2013
Health Authority:	Sweden: Centrala Etikprövningsnämnden

Keywords provided by GlaxoSmithKline:

Safety
Refractory
Chronic Lymphocytic Leukemia

Oncology
Ofatumumab
Efficacy

Additional relevant MeSH terms:

Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders

Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Fludarabine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 13, 2013